2-(3-pyridyl)-6-(4-bromophenylamino)-9-iso-propylpurine | 1056016-05-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 2-(3-pyridyl)-6-(4-bromophenylamino)-9-iso-propylpurine
• 英文别名: N-(4-bromophenyl)-9-propan-2-yl-2-pyridin-3-ylpurin-6-amine
• CAS: 1056016-05-7
• 化学式: C₁₉H₁₇BrN₆
• 分子量: 409.288
• InChiKey: KQOZMABNRXFRDT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  68.5
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-bromophenyl-(2-chloro-9-isopropyl-9H-purin-6-yl)amine 、 3-吡啶硼酸频哪醇酯 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 以26%的产率得到2-(3-pyridyl)-6-(4-bromophenylamino)-9-iso-propylpurine
  参考文献：
  名称：

  Roscovitine-Derived, Dual-Specificity Inhibitors of Cyclin-Dependent Kinases and Casein Kinases 1

  摘要：

  Cyclin-dependent kinases (CDKs) and casein kinases 1 (CK 1) are involved in the two key molecular features of Alzheimer's disease, production of amyloid-beta peptides (extracellular plaques) and hyper-phosphorylation of Tau (intracellular neurofibrillary tangles). A series of 2,6,9-trisubstituted purines, structurally related to the CDK inhibitor roscovitine, have been synthesized. They mainly differ by the substituent on the C-6 position. These compounds were screened for kinase inhibitory activities and antiproliferative effects. Several biaryl derivatives displayed potent inhibition of both CDKs and CK1. In particular, derivative 13a was a potent inhibitor of CDK1/cyclin B (IC50: 220 nM), CDK5/p25 (IC50: 80 nM), and CK1 (IC50: 14 nM). Modeling of these molecules into the ATP-binding pocket of CK1 delta provided a rationale for the increased selectivity toward this kinase. 13a was able to prevent the CK1-dependent production of anyloid-beta in a cell model. CDK/CK1 dual-specificity inhibitors may have important applications in Alzheimer's disease and cancers.

  DOI：

  10.1021/jm800109e

文献信息

• Roscovitine-Derived, Dual-Specificity Inhibitors of Cyclin-Dependent Kinases and Casein Kinases 1
  作者：Nassima Oumata、Karima Bettayeb、Yoan Ferandin、Luc Demange、Angela Lopez-Giral、Marie-Lorène Goddard、Vassilios Myrianthopoulos、Emmanuel Mikros、Marc Flajolet、Paul Greengard、Laurent Meijer、Hervé Galons

  DOI：10.1021/jm800109e

  日期：2008.9.11

  Cyclin-dependent kinases (CDKs) and casein kinases 1 (CK 1) are involved in the two key molecular features of Alzheimer's disease, production of amyloid-beta peptides (extracellular plaques) and hyper-phosphorylation of Tau (intracellular neurofibrillary tangles). A series of 2,6,9-trisubstituted purines, structurally related to the CDK inhibitor roscovitine, have been synthesized. They mainly differ by the substituent on the C-6 position. These compounds were screened for kinase inhibitory activities and antiproliferative effects. Several biaryl derivatives displayed potent inhibition of both CDKs and CK1. In particular, derivative 13a was a potent inhibitor of CDK1/cyclin B (IC50: 220 nM), CDK5/p25 (IC50: 80 nM), and CK1 (IC50: 14 nM). Modeling of these molecules into the ATP-binding pocket of CK1 delta provided a rationale for the increased selectivity toward this kinase. 13a was able to prevent the CK1-dependent production of anyloid-beta in a cell model. CDK/CK1 dual-specificity inhibitors may have important applications in Alzheimer's disease and cancers.